Pragmatic Free Trial Meta
Pragmatic Free Trail Meta is an open data platform that facilitates research into pragmatic trials. It shares clean trial data and ratings using PRECIS-2, which allows for multiple and varied meta-epidemiological research studies to evaluate the effect of treatment on trials that employ different levels of pragmatism as well as other design features.
Background
Pragmatic trials are increasingly recognized as providing real-world evidence to support clinical decision-making. The term "pragmatic", however, is used inconsistently and its definition and evaluation need further clarification. The purpose of pragmatic trials is to inform policy and clinical practice decisions, rather than to prove a physiological or clinical hypothesis. A pragmatic trial should aim to be as close as possible to real-world clinical practices, including recruiting participants, setting, designing, delivery and execution of interventions, determining and analysis outcomes, and primary analyses. This is a significant distinction from explanation trials (as described by Schwartz and Lellouch1), which are designed to provide more complete confirmation of the hypothesis.
The trials that are truly practical should not attempt to blind participants or healthcare professionals, as this may cause bias in estimates of treatment effects. Pragmatic trials should also seek to recruit patients from a variety of health care settings, to ensure that their findings can be compared to the real world.
Finally, pragmatic trials should focus on outcomes that are vital for patients, such as quality of life or functional recovery. This is especially important in trials that involve surgical procedures that are invasive or have potentially dangerous adverse events. The CRASH trial29, for example focused on the functional outcome to compare a 2-page case-report with an electronic system for monitoring of hospitalized patients with chronic heart failure, and the catheter trial28 used urinary tract infections caused by catheters as the primary outcome.
In addition to these aspects the pragmatic trial should also reduce the trial procedures and data collection requirements in order to reduce costs. Finaly the aim of pragmatic trials is to make their results as applicable to current clinical practices as they can. This can be accomplished by ensuring that their primary analysis is based on the intention to treat method (as defined in CONSORT extensions).
Many RCTs which do not meet the requirements for pragmatism but contain features contrary to pragmatism, have been published in journals of different kinds and incorrectly labeled pragmatic. This could lead to false claims of pragmatism and the usage of the term should be standardized. The creation of a PRECIS-2 tool that offers an objective, standardized assessment of pragmatic features is the first step.
Methods
In a pragmatic research study, the goal is to inform clinical or policy decisions by showing how an intervention can be integrated into routine treatment in real-world contexts. Explanatory trials test hypotheses regarding the causal-effect relationship in idealized settings. In this way, pragmatic trials could have less internal validity than explanatory studies and are more susceptible to biases in their design as well as analysis and conduct. Despite these limitations, pragmatic trials may contribute valuable information to decision-making in the context of healthcare.
The PRECIS-2 tool scores an RCT on 9 domains, ranging from 1 to 5 (very pragmatic). In this study, the recruitment, organization, flexibility in delivery and follow-up domains scored high scores, but the primary outcome and the method of missing data fell below the limit of practicality. This suggests that it is possible to design a trial using high-quality pragmatic features, without compromising the quality of its results.
It is, however, difficult to determine how pragmatic a particular trial is, since pragmatism is not a binary quality; certain aspects of a study can be more pragmatic than others. The pragmatism of a trial can be affected by modifications to the protocol or logistics during the trial. Koppenaal and colleagues found that 36% of the 89 pragmatic studies were placebo-controlled, or conducted prior to licensing. Most were also single-center. They are not in line with the norm and are only called pragmatic if their sponsors agree that these trials aren't blinded.
Another common aspect of pragmatic trials is that the researchers try to make their results more relevant by analyzing subgroups of the trial sample. However, this often leads to unbalanced results and lower statistical power, increasing the chance of not or misinterpreting differences in the primary outcome. In the case of the pragmatic trials included in this meta-analysis, this was a major issue because the secondary outcomes were not adjusted to account for variations in baseline covariates.
Additionally the pragmatic trials may be a challenge in the gathering and interpretation of safety data. This is because adverse events are usually self-reported and are prone to reporting delays, inaccuracies, or coding variations. It is important to improve the quality and accuracy of the outcomes in these trials.
Results
While the definition of pragmatism may not require that all clinical trials are 100% pragmatist there are benefits of including pragmatic elements in trials. These include:
Increasing sensitivity to real-world issues which reduces the size of studies and their costs and allowing the study results to be more quickly transferred into real-world clinical practice (by including patients from routine care). However, pragmatic trials can also have drawbacks. For example, the right type of heterogeneity could help a trial to generalise its findings to a variety of settings and patients. However the wrong kind of heterogeneity could reduce assay sensitivity and therefore lessen the ability of a trial to detect small treatment effects.
A variety of studies have attempted to categorize pragmatic trials, with a variety of definitions and scoring systems. 프라그마틱 슬롯 추천 and Lellouch1 have developed a framework that can differentiate between explanation studies that support a physiological or clinical hypothesis, and pragmatic studies that guide the choice for appropriate therapies in clinical practice. The framework was comprised of nine domains that were scored on a scale of 1 to 5, with 1 being more informative and 5 suggesting more pragmatic. The domains were recruitment setting, setting, intervention delivery with flexibility, follow-up and primary analysis.
The original PRECIS tool3 featured similar domains and an assessment scale ranging from 1 to 5. Koppenaal et al10 created an adaptation of this assessment called the Pragmascope that was easier to use in systematic reviews. They found that pragmatic systematic reviews had a higher average score in most domains but lower scores in the primary analysis domain.
This difference in primary analysis domain can be due to the way in which most pragmatic trials analyze data. Certain explanatory trials however do not. The overall score was lower for systematic reviews that were pragmatic when the domains of the organization, flexibility of delivery and follow-up were combined.
It is important to understand that the term "pragmatic trial" does not necessarily mean a low-quality trial, and indeed there is an increasing number of clinical trials (as defined by MEDLINE search, however this is neither specific nor sensitive) which use the word 'pragmatic' in their abstracts or titles. These terms may signal a greater understanding of pragmatism in abstracts and titles, however it isn't clear whether this is evident in the content.
Conclusions
As the importance of real-world evidence grows widespread the pragmatic trial has gained popularity in research. They are randomized trials that evaluate real-world care alternatives to experimental treatments in development. They involve patient populations more closely resembling those treated in regular care. This method has the potential to overcome limitations of observational studies that are prone to biases that arise from relying on volunteers, and the limited accessibility and coding flexibility in national registry systems.
Pragmatic trials have other advantages, such as the ability to draw on existing data sources and a greater chance of detecting significant differences from traditional trials. However, they may still have limitations which undermine their effectiveness and generalizability. For instance the rates of participation in some trials might be lower than anticipated due to the healthy-volunteer effect and incentives to pay or compete for participants from other research studies (e.g., industry trials). Practical trials are often limited by the need to enroll participants on time. Certain pragmatic trials lack controls to ensure that the observed differences aren't caused by biases during the trial.
The authors of the Pragmatic Free Trial Meta identified RCTs published up to 2022 that self-described as pragmatic. The PRECIS-2 tool was employed to determine the degree of pragmatism. It includes domains such as eligibility criteria, recruitment flexibility, adherence to intervention, and follow-up. They found 14 trials scored highly pragmatic or pragmatic (i.e. scoring 5 or higher) in at least one of these domains.
Trials that have a high pragmatism score tend to have more expansive eligibility criteria than traditional RCTs which have very specific criteria that are unlikely to be found in the clinical environment, and they include populations from a wide range of hospitals. According to the authors, can make pragmatic trials more useful and relevant to the daily clinical. However, they don't ensure that a study is free of bias. In addition, the pragmatism that is present in the trial is not a fixed attribute and a pragmatic trial that does not have all the characteristics of a explanatory trial may yield valid and useful results.